PRELIMINARY EVIDENCE THAT AUGMENTATION THERAPY DIMINISHES DEGRADATIONOF CROSS-LINKED ELASTIN IN ALPHA-1-ANTITRYPSIN-DEFICIENT HUMANS

It is hypothesized that emphysema develops in some severely alpha(1)-a ntitrypsin (AAT)-deficient persons because endogenous elastases are no t adequately controlled by AAT, and accelerated elastin degradation oc curs. It is not known whether augmentation therapy with AAT diminishes degradation of lung elastin in severely deficient persons with lung d isease. Two severely deficient, PiZ patients were studied, a 63-year-o ld never-smoking woman with bronchiectasis and a 41-year-old smoking m an with emphysema. Urinary desmosine (DES) was determined before and a fter augmentation therapy with AAT, 260 mg/kg/month. Mean +/- SEM pret reatment urinary DES was elevated in both patients, 19.7 +/- 0.9 (n = 2) and 10.8 +/- 0.2 (n = 2) mu g/g creatinine, respectively, compared to normal values of 7.5 +/- 0.3 (n = 22) mu g/g creatinine. Following augmentation therapy, urinary DES values decreased 40 and 36%, respect ively, to 11.9 +/- 0.3 (n = 8) and 6.9 +/- 0.4 (n = 7) mu g/g creatini ne (p < 0.05). We conclude that monthly AAT augmentation therapy decre ased DES excretion in the urine of these PiZ patients. We speculate th at since there was lung disease in both patients, a decrease in degrad ation of lung elastin is the most likely explanation for this observat ion.